Dystrophin-deficient skeletal (DMD) muscle is highly susceptible to oxidative damage, however, it remains unknown whether oxidative stress contributes to muscle death in non-dystrophin-deficient types of muscular dystrophies (LGMD). Oxidative damage to macromolecules can lead to modification to proteins, lipids, and nucleic acids resulting in cellular dysfunction and death. Catalase, an antioxidant enzyme that converts hydrogen peroxide into water and oxygen, may play a key role in counteracting oxidative stress-induced muscle damage. Preliminary findings suggest that oxidative stress plays a significant role in muscle death in LGMD 11C (lack dystrophin-glycoprotein associated complex protein, gamma sarcoglycan) mice and studies are ongoing investigating the presence of oxidative stress in LGMD II (lack plasma membrane repair protein, dysferlin) mice. It is hypothesized that preliminary findings in LGMD IIC will be confirmed and oxidative damage will be present in this model as well as other models of LGMD such as LGMD II. Further, it is hypothesized that anti-oxidant administration will reduce muscle dysfunction and improve the appearance of both DMD and LGMD muscle. While it has been demonstrated that apoptosis likely does not contribute to disease pathology in the mdx mouse, the contribution of apoptosis to disease pathology in LGMD remains unknown. It is hypothesized that inhibition of apoptosis by anti-apoptotic factor Bcl-2 will improve muscle function and appearance in models of LGMD. To test these hypotheses, models of LGMD that have increased oxidative damage and/or increased apoptosis will be identified. Next, a catalase over- expression adeno-associated virus (AAV) and/or Bcl-2 over-expression AAV will be created and delivered to young mice prior to disease onset. Studies in both DMD and LGMD will determine if enhanced catalase expression and/or Bcl-2 expression can slow progression of dystrophic pathology. In addition to a detailed histological examination, an assessment of ex vivo muscle function will also be employed to determine the effectiveness of treatments. It is anticipated that early anti-oxidant and/or anti-apoptotic intervention will be effective therapeutic strategies. The muscular dystrophies are a collection of muscle pathologies related to dysfunction of the dystrophin- glycoprotein complex, usually due to an absent protein. Depending on the pathology type, these patients are wheel chair bound by the early teens and die in the early twenties. Currently, no known cure is available and therapies, such as those proposed here, are welcomed by the muscular dystrophy community as they alleviate disease pathology and ultimately prolong mobility and life. [unreadable] [unreadable] [unreadable] [unreadable]